The enantioselective reduction of prochiral ketones to give optically active alcohols has been extensively studied, and several reagents have been developed for this transformation. For example, Corey (U.S. Pat. No. 4,943,635) and Blacklock et al. (U.S. Pat. No. 5,039,802) have disclosed one series of oxazaborolidine catalysts derived from (S)- or (R)-2-(diphenylhydroxy methyl)pyrrolidine. These oxazaborolidines are disubstituted at the carbon atom attached directly to the oxygen atom of the oxazaborole, and it has been observed that when the .alpha.-carbon atom is not disubstituted, the enantioselectivity of the reduction is much lower. [See Martens, et al., Tetrahedron: Asymmetry 3, 347-350 (1992).]
Didier, et al., [Tetrahedron, 47, 4941-4958 (1991)] have studied the enantioselective reduction of acetophenone and the corresponding oxime methyl ether with borane in the presence of chiral amino alcohols including cis-1-amino-2-indanol. Didier stated that, under the conditions of their reaction, "With stoichiometric amounts of the ligand, all the reductions of acetophenone required more time than the reduction with borane alone . . . Consequently no system was found to be efficient with catalytic amounts of ligand." They concluded that "it seems, as shown in previous works, that disubstitution in [the] .alpha.-position of the hydroxyl group was necessary to attain high selectivities as well as good catalytic effects."
Quallich has disclosed a new class of oxazaborolidine catalysts derived from optically pure 1,2-diphenyl-2-aminoethanols [PCT WO 93/23408; Tetrahedron Lett 34, 4145-4148 (1993) and Synlett 1993, 929].
The known methods suffer from one or more of the following drawbacks: (a) unacceptable amounts of the undesired enantiomer present as an impurity with the product; (b) low yields of alcohol; (c) difficulty of carrying out the reaction; (d) expense of preparing the catalyst; (e) difficulty in preparing the catalyst; or (f) inapplicability to a wide range of substituted prochiral ketones.
It is therefore an object of this invention to provide chiral oxazaborolidine compounds which are capable of directing the enantioselective reduction of prochiral ketones to generate substantially enantiomerically pure alcohols.
It is a further object of this invention to provide chiral oxazaborolidine compounds which are easily prepared from relatively inexpensive starting materials or readily available starting materials.
It is a still further object of this invention to provide a method of using these chiral oxazaborolidine compounds as catalysts for the enantioselective reduction of prochiral ketones to afford substantially enantiomerically pure alcohols.